Basal cell carcinoma (BCC) is the most common skin cancer. Its incidence is increasing in many countries throughout the world, for example, in Sweden. Long-term immunosuppression, e.g. after allogeneic organ transplantation, increases the risk of developing BCC and other skin tumours. This is also the case following exposure to ultraviolet light or ionizing radiation. There seems to be no apparent genetic connection and in many patients no other predisposing factors are found. However, clinical diagnosis of skin tumours can prove difficult even for experienced dermatologists, especially in the case of pigmented lesions. In the clinic there is a need for a diagnostic aid besides the established naked eye in combination with skin biopsies for histological examination.
Non-invasive methods of making biological determinations, such as clinical diagnosis of skin tumours, are generally desirable over invasive techniques that involve the taking of samples. Non-invasive techniques can be more convenient, e.g. less painful, involve less risk of infection etc. Accordingly, a number of non-invasive techniques for making biological determinations have been proposed:
Application No.Publication NoPublication dateNameU.S. Pat. No. 5,036,861Aug. 6, 1991Sembrowich et al.U.S. Pat. No. 5,115,133May 19, 1992KnudsonU.S. Pat. No. 5,146,091Sep. 8, 1992KnudsonU.S. Pat. No. 5,197,951Jan. 19, 1993Knudson.U.S. Pat. No. 5,222,496Jun. 29, 1993Clarke et al.PCT/US94/08816WO95/04496Feb. 16, 1995Solid State Farms, inc.U.S. Pat. No. 5,433,197Jul. 18, 1995StarkPCT/US97/13267WO 98/04190Feb. 5, 1998Dermal Therapy (Barbados) Inc.PCT/US98/02037WO 99/39627Aug. 12, 1999Dermal Therapy (Barbados) Inc.PCT/IB00/01464WO 01/26338Oct. 13, 2000Süsstrunk, et al.
However, all of the above-mentioned documents disclose techniques for evaluating blood glucose levels and are consequently not suitable for diagnosing a diseased condition of the skin of a subject, particularly the presence of skin cancer, e.g. basal cell carcinoma.
Electrical impedance has been found to constitute a very sensitive indicator of minute changes in organic and biological material and especially tissues such as mucous membranes, skin and integuments of organs and, hence, provides an effective tool for non-invasive measurements of variations in structural properties of the tissue. In PCT/SE91/00703 a device for non-invasive measurement of electrical impedance of organic and biological material is disclosed. A probe comprising a number of electrodes arranged in a concentric ring system. The electrodes are driven from a control unit in such a way that the electric current path defining the actual tissue under test is dependent upon a control signal, is pressed towards the surface of the body part under test. By varying the control signal it is possible to select the region under test. Two rings supply voltage and the relation between the two will generate a virtual projection point located between the two rings. By adjusting the voltage relation between the two injection points the virtual injection point can be moved back and forth and hence the depth penetration in the tissue is selectable. However, human skin is a complex, heterogeneous, and anisotropic multilayer structure with electronically non-linear properties. The most non-linear properties are located to the Stratum Corneum (the outermost layer of epidermis). Therefore, there is information in all depth measurements that cannot be calculated by interpolation or extrapolation from two depths although the different depths are highly correlated. However, the device disclosed in PCT/SE91/00703 is impaired with a severe drawback in that it cannot deliver reliable results regarding tissue variation in skin layers beneath stratum corneum where, for example, skin cancer and allergic reactions manifest. This is due to the fact that non-invasive electrical impedance spectra of skin are dominated by the dielectric properties of the Stratum Corneum, especially at low frequencies. The stratum corneum has properties (a large and broad so called alpha dispersion) that may lead to that responses from underlying viable skin layers is confounded with responses from stratum corneum, thus diluting the clinically relevant information from the viable skin. This makes it difficult and unpredictable to assess electrical impedance phenomena that manifest below the stratum corneum using the probe disclosed in PCT/SE91/00703.
WO 01/52731 discloses a medical electrode for sensing electric biopotentials created within the body of a living subject. The electrode comprises a number of micro-needles adapted to penetrate the skin. The micro-needles are long enough to reach the stratum germinativum and are electrically conductive on their surface and connected to each other to form an array. According to WO 01/52731, the micro-needles are “nail-like”, i.e. they have stem having a substantially circular cross-section with a constant or a gradually decreasing diameter and a tip-portion with a substantially spherical or needle-shaped tip. In EP 1 437 091 an apparatus for diagnosis of biological conditions using impedance measurements of organic and biological material is disclosed. The apparatus comprises a probe including a plurality of electrodes, where each electrode is provided with a number of micro-needles each having a length being sufficient to penetrate stratum corneum. The micro-needles according to EP 1 437 091 are also “nail-like”, i.e. they have stem having a substantially circular cross-section with a constant or a gradually decreasing diameter and a tip-portion with a substantially spherical or needle-shaped tip.
However, practical experience has shown that electrodes furnished with micro-needles according to the conventional technique requires a substantial force or requires a significant manipulating, for example, tilting the electrode to and fro, in order to obtain a proper penetration of the micro-needles into the stratum germinativum. This may be uncomfortable and cumbersome for the patient as well as for the operator, e.g. a physician or a nurse, performing the test. Moreover, this may also require that the needles are construed with a sufficient strength by increasing its size in order to avoid the possibility of needle breakage during use.
Thus, there is a need of an improved medical electrode, apparatus for a non-invasively diagnosing a diseased condition of the skin of a subject, particularly the presence of skin cancer, e.g. basal cell carcinoma or malignant melanoma, a squamous cell carcinoma or precursors thereof.